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Efficacy of monoterpene perillyl alcohol upon survival rate of patients with recurrent glioblastoma

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Abstract

Purpose

The monoterpene perillyl alcohol (POH) a Ras inhibitor with potential capacity to arrest gliomagenesis is being used in a phase I/II clinical trial in adults with recurrent malignant glioma. The present study aimed to investigate the efficacy of intranasal administration of monoterpene POH upon survival rate of patients with recurrent glioblastoma (GBM) in comparison with historical control group of GBM patients.

Patients and methods

It was included 89 adults with recurrent GBM receiving daily intranasal administration of 440 mg POH and 52 matched GBM patients as historical control untreated group only with supportive treatment.

Results

Patients with recurrent primary GBM treated with POH survived significantly longer (log rank test, P < 0.0001) than untreated group. Patients with recurrent primary GBM in deep location survived significantly longer than with lobar location (log rank test, P < 0.0001). Median survival rate of secondary GBM was 11.2 months, longer (log rank test, P = 0.0366) than primary GBM (5.9 months). Radiographic improvement and reduction of corticosteroid dosage (36%) further associated with a delay towards progression.

Conclusion

Intranasal administration of POH increased the overall survival of patients with recurrent GBM in comparison with historical untreated controls, but especially patients with secondary GBM and primary GBM with tumor localized in deep regions of the brain. The side effects of POH treatment were almost nonexistent, even in patients treated for over 4 years.

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Acknowledgments

This study was supported by grants from FAPERJ (Fundação de Amparo a Pesquisa do Rio de Janeiro, number: E-26/111.425/2008) and CNPq (Brazilian Research Council number: 470441/2008-9). We thank Marcela d’Allincourt Salazar from the Biochemistry and Cancer Biology program of The University of Toledo, Ohio, USA for general discussion and critical reading of the manuscript and the pathologist Janaina Nagel for histological analysis and Silvana da Silva Souza for technical assistance with the intranasal formulation of perillyl alcohol and Adriano Arnobio for the statistical analysis.

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Authors and Affiliations

  1. Departamento de Cirurgia Geral e Especializada, Unidade de Pesquisa Clínica, Hospital Universitário Antonio Pedro, Niterói, RJ, 24030-210, Brazil

    Clovis O. da Fonseca

  2. Department of General and Specialized Surgery, Clinical Research Unit - Antonio Pedro University Hospital, Fluminense Federal University, Niterói, RJ, Brazil

    Clovis O. da Fonseca & Igor R. Lins

  3. Laboratory of Cellular Pathology, Department of Cellular and Molecular Biology, Institute of Biology, Fluminense Federal University, Niterói, RJ, Brazil

    Marcela Simão, Regina O. Caetano & Thereza Quirico-Santos

  4. Department of Pharmaceutical Sciences, School of Pharmacy, Fluminense Federal University, Niterói, RJ, Brazil

    Débora Futuro

Authors
  1. Clovis O. da Fonseca
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  2. Marcela Simão
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  3. Igor R. Lins
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  4. Regina O. Caetano
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  5. Débora Futuro
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  6. Thereza Quirico-Santos
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Corresponding author

Correspondence to Clovis O. da Fonseca.

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da Fonseca, C.O., Simão, M., Lins, I.R. et al. Efficacy of monoterpene perillyl alcohol upon survival rate of patients with recurrent glioblastoma. J Cancer Res Clin Oncol 137, 287–293 (2011). https://doi.org/10.1007/s00432-010-0873-0

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  • DOI: https://doi.org/10.1007/s00432-010-0873-0

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